Structural Control of Membrane-Targeted Peptides for Delivery of Functional Proteins

Abstract

The plasma membrane controls the flow of bioactive molecules entering the cell. Most small molecules can easily cross plasma membranes. However, macromolecules such as proteins or antibodies with pharmacological characteristics have limited access, either by hindering internalization or endosomal escape. Therefore, during the development of this PhD thesis we designed new CPPs as transporters of this type of drugs. We investigated new CPP designs and how to modulate their cellular activity, penetration and viability capabilities. Starting with new peptide libraries through dynamic linkages to discover good ratios between cationic charge and hydrophobic residues. Moving on to designs that increase helical folding in membranes to improve internalization and viability. Finally, to characterize the supramolecular behavior in membranes of the designed CPPs and to evaluate the capacity for transport and delivery of protein drugs.